What is the role of nitrates in patients with Aortic Stenosis (AS) or Aortic Regurgitation (AR)?

Nitrates in Aortic Stenosis and Aortic Regurgitation

Aortic Stenosis

Nitrates can be used cautiously in patients with aortic stenosis, particularly for acute pulmonary edema, but require strict blood pressure monitoring and should be avoided when systolic blood pressure is below 90 mmHg. 1

Blood Pressure-Based Algorithm for Nitrate Use in AS

• Systolic BP <90 mmHg: Nitrates are absolutely contraindicated—they reduce preload and can critically compromise cardiac output across the fixed stenotic valve, potentially causing cardiovascular collapse 2, 1

• Systolic BP 90-110 mmHg: Use nitrates with extreme caution and consider alternative therapies first; if used, continuous arterial line monitoring is recommended 1

• Systolic BP >110 mmHg with acute pulmonary edema: Nitrates are recommended and can be safely administered with appropriate monitoring 1, 2

Mechanism and Rationale in AS

The traditional teaching that nitrates are contraindicated in severe AS stems from concern about fixed outflow obstruction making patients sensitive to preload reduction 1. However, recent evidence challenges this dogma:

• Nitrates reduce left ventricular end-diastolic pressure and can improve valvulo-arterial impedance, thereby reducing LV work 2

• In patients with severe AS, reduced LV function, and congestive heart failure, nitroprusside has demonstrated enhanced perfusion and augmented cardiac indices 2

• A retrospective study of AS patients with acute pulmonary edema found no association between nitrate administration and clinically relevant hypotension 2

• A 2015 study of 195 episodes of acute pulmonary edema (including 65 with severe AS) found no increased risk of clinically relevant hypotension with nitroglycerin use (adjusted OR 0.99,95% CI 0.41-2.41) 3

Practical Application in AS

For acute pulmonary edema with AS and SBP >110 mmHg: Start intravenous isosorbide dinitrate at 1-10 mg/h with careful titration based on blood pressure response 1

• Target a reduction of approximately 10 mmHg in mean arterial pressure 1

• Continuous monitoring of blood pressure, heart rate, respiratory rate, and oxygen saturation is mandatory 1

• Consider arterial line placement for borderline blood pressure cases 1

Critical Contraindications Beyond Blood Pressure

• Recent phosphodiesterase-5 inhibitor use (within 24 hours for sildenafil/vardenafil, 48 hours for tadalafil) 1, 2

• Right ventricular infarction—these patients are preload-dependent and nitrates can cause catastrophic hypotension 1, 2

• Severe bradycardia (<50 bpm) or tachycardia (>100 bpm) without symptomatic heart failure 1

Important Caveats for AS

• Exercise extreme caution when combining nitrates with ACE inhibitors or ARBs, as the combination potentiates hypotension 1

• Loop diuretics should also be used cautiously in severe AS with LV hypertrophy and small ventricular cavities, as abrupt volume changes may cause significant hypotension 2

• Nitrate efficacy may diminish after 16-24 hours due to tachyphylaxis; consider transitioning to oral nitrates with a nitrate-free interval after stabilization 1

• The role of nitrates in chronic AS management remains unclear, though adverse effects are likely more theoretical than proven 2

Aortic Regurgitation

Vasodilators including nitrates play a therapeutic role in chronic AR by reducing afterload and regurgitant volume, but their primary indication is for managing systemic hypertension and delaying surgery in asymptomatic patients with normal LV function. 4

Mechanism in AR

The pathophysiology of chronic AR involves progressive LV pressure and volume overload with systolic hypertension and wide pulse pressure 4. Vasodilators address this by:

• Reducing systolic arterial pressure and afterload excess 4

• Decreasing regurgitant volume 2

• Minimizing adverse LV remodeling 4

Clinical Application in AR

Unlike AS, vasodilators are beneficial in chronic severe AR for patients who:

• Are asymptomatic with normal LV function but require medical management to delay surgery 4

• Have systemic hypertension requiring control 2

• Are not surgical candidates due to comorbidities 4

Surgical Timing Considerations

Surgery should be performed before:

• LV ejection fraction falls below 55% 4
• LV end-systolic dimension reaches 55 mm 4
• Development of symptoms 4

Acute AR vs Chronic AR

Acute AR is a surgical emergency causing severe pulmonary edema and hypotension; medical management with vasodilators is a temporizing measure only while preparing for urgent surgery 4

AR-Specific Cautions

The same blood pressure and contraindication principles apply as in AS, though AR patients typically tolerate vasodilators better due to the absence of fixed outflow obstruction 2. However, nitrates should still be avoided with SBP <90 mmHg or in the presence of RV infarction 2.